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Biomedical subjects

J Parratt

Publications and source records attributed to J Parratt.

17 recordsLinked to original sources

Pacing-induced delayed protection against arrhythmias is attenuated by aminoguanidine, an inhibitor of nitric oxide synthase.

1. Cardiac pacing, in anaesthetized dogs, protects against ischaemia and reperfusion-induced ventricular arrhythmias when this is initiated 24 h after the pacing stimulus. Now we have examined whether this delayed cardioprotection afforded by cardiac pacing is mediated through nitric oxide. 2. Twenty-two dogs were paced (4 x 5 min periods at 220 beats min(-1)) by way of the right ventricle, 24 h prior to a 25 min period of coronary artery occlusion. Nine of these dogs were given the inhibitor of induced nitric oxide synthase, aminoguanidine (50 mg kg(-1) i.v.), 0.5 h prior to coronary artery occlusion. Sham-operated non-paced dogs with and without aminoguanidine treatment served as controls. 3. Pacing markedly (P<0. 05) reduced arrhythmia severity (ventricular fibrillation, VF, during occlusion 15%; survival from the combined ischaemia-reperfusion insult 62%) compared to control, sham-operated, unpaced dogs (VF during occlusion 58%; survival 17%). This protection was attenuated by the administration of aminoguanidine prior to coronary artery occlusion (survival from the combined ischaemia-reperfusion insult 11%, which was significantly (P<0.05) less than in the paced dogs not given aminoguanidine and similar to the controls). Aminoguanidine had no significant effects on coronary artery occlusion when given to dogs that had not been paced. In the dose used aminoguanadine transiently elevated systemic arterial pressure by a mean of 20 mmHg and reduced heart rate by a mean of 22 beats min(-1). 4. These results suggest that nitric oxide, probably derived from induced nitric oxide synthase, contributes significantly to the delayed cardioprotection afforded by cardiac pacing.

Animals↗

Confronting Y2K physician practice guidelines.

The year 2000 computer problem is primarily a result of a programming technique called two-digit date processing. This technique reduced dates from eight digits to six digits, as programmers assumed the first two digits in every year would be 19. Software, hardware, and other computer equipment may not recognize or process the date properly when the year changes this coming January.

Chronology as Topic↗

Practising midwifery independently: for the majority of midwives?

This paper explores the proposition that all midwives can practice independently regardless of their place of practice or employment status. That independence can be defined by the way in which the midwife practises is discussed. The theory of midwifery as a partnership is reviewed and its effects on midwifery as a profession will be explored. How this relates to Victoria and the absence of regulations will also be discussed. The need for continuity of care and women centred practice will be analysed in this context. Advocacy, as used by midwives, will be examined, as will midwife empowerment of the woman and the midwife.

Australia↗

Abolition of contractions in the myometrium by acidification in vitro.

Uterine dystocia, often of unknown cause, remains one of the commonest causes of emergency caesarean section. We have tested the hypothesis that small acidic changes in pH, that can occur during labour contractions, can decrease contractions and contribute to dystocia. We simultaneously recorded intracellular pH (pHi) and force in human myometrium: acidification abolished contractions. Such effects of pHi on uterine contractile activity may be of clinical significance. Blood flow reduces during each uterine contraction; the resulting fall in pHi could lead to inefficient uterine action in some labours and failure to progress (ie, dystocia).

Adult↗

The experience of childbirth for survivors of incest.

The purpose of this research was to discover what experiences, including feelings, women who are survivors of incest have during childbirth. The recognition that the childbirth experience may trigger memories of incest that will then alter the course of childbirth was the framework for the study. This exploratory research was undertaken using a phenomenological approach. The six participants were obtained through networking and issues surrounding confidentiality and consent were of a high priority. The data consists of transcripts of taped, one to two hour, in-depth interviews. During interviews each woman recalled her experiences and feelings during and surrounding childbirth. Qualitative analysis was undertaken, the findings indicating that memories of previous abuse may be provoked by childbirth but that it is a very individualised response. The effect of these memories on the childbirth experience is also variable but does occur. Privacy, control and touch are important aspects of these women's childbirth experiences. The results and interpretation of findings presented in this report centre around the labour and delivery experiences of the women. The variety of women's needs demonstrated in this project emphasise the importance of individualised care by midwives and doctors involved in the care of childbearing women.

Adult↗

Attenuation of the antiarrhythmic effects of ischaemic preconditioning by blockade of bradykinin B2 receptors.

1. The possibility that bradykinin is involved in the pronounced antiarrhythmic effects of ischaemic preconditioning in anaesthetized mongrel dogs was examined with the use of the selective B2 antagonist, icatibant (Hoe-140). 2. Preconditioning, achieved by two 5 min occlusions of the left anterior descending coronary artery, followed 20 min later by a 25 min occlusion of the same artery resulted, during this prolonged occlusion, in less severe arrhythmias (VF 0% versus 47% in control non-preconditioned dogs), reductions in the incidence and number of episodes of ventricular tachycardia (VT) and in the number of ventricular premature beats and increased survival following reperfusion (50% versus 0% in the controls). 3. Hoe-140 was given in a dose of 300 micrograms kg-1 either before the preconditioning procedure or after preconditioning but before the prolonged occlusion. This dose of Hoe-140 had insignificant haemodynamic effects and failed to modify the increase in coronary blood flow that occurred in the circumflex coronary artery when the anterior descending branch was occluded. 4. It was difficult to precondition dogs in the presence of Hoe-140. There were more ventricular arrhythmias during the initial 5 min occlusion (44 +/- 12 versus 10 +/- 3) and a higher incidence of ventricular fibrillation (50% versus 21%) during the preconditioning procedure. There was also a more pronounced ST-elevation (recorded from epicardial electrodes) during the preconditioning occlusions in those dogs given Hoe-140. 5. In those dogs that survived to the long (25 min) occlusion, Hoe-140 prevented the antiarrhythmic effects of preconditioning (reduction in ventricular premature beats and in VT) although all the dogs survived the occlusion period. However on reperfusion, survival in the preconditioned dogs given Hoe-140 was less than in those dogs preconditioned without the B2 antagonist.6. Changes in the degree of inhomogeneity of conduction within the ischaemic area, which were markedly suppressed by preconditioning, were attenuated in those dogs preconditioned in the presence of Hoe-140.7. These results suggest that bradykinin acts as both a 'trigger' for preconditioning and as one of the mediator protective (antiarrhythmic) substances generated by the myocardium under these conditions.Since the protection afforded both by preconditioning and by local intracoronary infusions of bradykinin is markedly attenuated by an inhibitor of the L-arginine nitric oxide pathway, we suggest that much of the protection afforded by ischaemic preconditioning results from the generation of nitricoxide, and that bradykinin, released early during ischaemia, acts as a stimulant for this generation.

Animals↗

Pronounced antiarrhythmic effects of ischemic preconditioning.

Brief periods of ischemia, induced either by complete coronary artery occlusion or by rapid ventricular pacing, greatly reduce the severity of those live-threatening ventricular arrhythmias that occur during a subsequent more prolonged occlusion of a major branch of the left coronary artery. The increased tolerance achieved by brief ischemia, either regional or global, has been termed ischemic preconditioning. This was originally defined as the reduction in ultrastructural changes and infarct size resulting from coronary artery occlusion and reperfusion by prior, brief, usually multiple ischemic periods. The reduction in the severity of arrhythmias by preconditioning, which has been described in several different species using both in vivo and in vitro models, depends on the duration and number of the short preconditioning occlusions and also on the time between the preconditioning period and the subsequent prolonged coronary artery occlusion. Under optimal conditions the antiarrhythmic effect of ischemic preconditioning is as pronounced as that with standard antiarrhythmic drugs. Unfortunately, the protection if also short-lived (usually less than 1 hour). If, however, we understood the precise mechanisms involved, we might be able to exploit them to ultimate therapeutic advantage. At least in the dog, the evidence suggests that the protection involves the release (from coronary vascular endothelial cells?) of endogenous myocardial protective substances such as bradykinin, nitric oxide and prostacyclin.

Animals↗

Effects of selective opioid receptor agonists and antagonists during myocardial ischaemia.

The antiarrhythmic activities of 16-methylcyprenorphine (M8008), nor-binaltorphimine (NBT) and naltrexone, which are relatively specific opioid receptor antagonists for delta, kappa and mu receptors, respectively, were examined during the 30 min following coronary artery occlusion in anaesthetised rats. The haemodynamic and electrocardiographic effects of the opioid receptor agonists [D-Ala2,D-Leu5]enkephalin (DADLE) (relatively selective for delta receptors), ICI-204448 (kappa) and glyol (mu) were also investigated over the 30-90 min post ligation period. When administered intravenously 5 min before ligation, M8008 (0.5 mg kg-1 and 2.5 mg kg-1) reduced the number of ventricular ectopic beats but had no effect on the incidence or duration of ventricular fibrillation. NBT and naltrexone were not antiarrhythmic at a dose of 0.5 mg kg-1 but at 2.5 mg kg-1 (a concentration at which both drugs block kappa receptors) the number of ventricular ectopic beats, the incidence of ventricular fibrillation and mortality were all reduced. All of the opioid receptor agonists caused a transient decrease in heart rate and in arterial blood pressure but none exhibited an arrhythmogenic effect. These studies suggest that the delta and kappa opioid receptor antagonists used may be antiarrhythmic as a result of blockade of the action of endogenously released peptides acting on these receptors or that they have a non-specific 'direct' antiarrhythmic action.

Animals↗

The electrophysiological effects of opioid receptor-selective antagonists on sheep Purkinje fibres.

The cardiac electrophysiological effects of 16-methylcyprenorphine (M8008), nor-binaltorphimine (NBT) and naltrexone, which are relatively specific opioid antagonists for delta, kappa and mu receptors, respectively, were studied in paced (1.5 Hz) sheep Purkinje fibres in vitro. M8008 (1 ng ml-1-10 micrograms ml-1) caused a concentration-dependent reduction in the maximum rate of depolarisation of phase 0 (MRD) and in the action potential duration measured at 50% repolarisation, APD50. Neither NBT (10 ng ml-1-10 micrograms ml-1) nor naltrexone (1 ng ml-1-10 micrograms ml-1) produced any significant effect on the cardiac action potential. In the presence of a physiological salt solution modified to mimic some of the changes that occur during myocardial ischaemia (i.e. hypoxia, acidosis, hyperkalaemia), M8008 caused a more marked reduction in MRD and prolonged rather than shortened APD50. These results suggest that the reported antiarrhythmic activity of M8008, but not NBT or naltrexone, may be, at least in part, explained by a direct cardiac electrophysiological action.

Acidosis↗

The local intracoronary administration of methylene blue prevents the pronounced antiarrhythmic effect of ischaemic preconditioning.

Short periods of coronary artery occlusion (2 x 5 min) markedly reduce the severity of arrhythmias and the changes in ST-segment elevation and in the degree of inhomogeneity of conduction during a subsequent 25 min occlusion of the left anterior descending coronary artery in anaesthetized dogs. These changes were completely reversed if methylene blue (5 mg min-1) was infused into a side branch of the coronary artery throughout both the preconditioning and prolonged occlusions. These results suggest that the pronounced antiarrhythmic effects of preconditioning result from activation of guanylyl cyclase and result in increased levels of guanosine 3':5'-cyclic monophosphate.

Animals↗

Preconditioning of the ischaemic myocardium; involvement of the L-arginine nitric oxide pathway.

1. Short periods of coronary artery occlusion protect the heart against the effects of a subsequent prolonged period of ischaemia. This phenomenon is known as preconditioning of the ischaemic myocardium. 2. In mongrel, chloralose-urethane anaesthetized open-chest dogs, within a restricted body weight range, two 5 min periods of occlusion of the anterior descending branch of the left coronary artery markedly reduced the severity of the early ischaemic arrhythmias resulting from a prolonged (25 min) occlusion of the same coronary artery starting 20 min later. Thus, the number of ventricular premature beats (VPBs) was reduced from 528 +/- 140 in controls to 78 +/- 27 in preconditioned dogs, the incidence of ventricular fibrillation (VF) was reduced from 47% to 0% and the incidence of ventricular tachycardia (VT) from 100% to 20%. ST-segment elevation recorded from electrodes within the ischaemic area, and the degree of inhomogeneity of conduction within the ischaemic area were markedly reduced in these preconditioned dogs. 3. The incidence of VF following reperfusion of the ischaemic myocardium at the end of the 25 min occlusion period was reduced in the preconditioned dogs from 100% to 60%; there was thus a 40% survival from the combined ischaemia-reperfusion insult compared with 0% in the controls. 4. NG-nitro-L-arginine methyl ester (L-NAME) an inhibitor of the L-arginine nitric oxide pathway, given in a dose of 10 mg kg-1 intravenously on two occasions, both before the initial preconditioning occlusion and then again before the prolonged occlusion, partially attenuated the protective effects of preconditioning.There were more VPBs (220 +/- 75), a higher incidence of VT (60%) and more episodes of VT (11.5 +/- 6.0 compared to 0.7 +/- 0.3 episodes in the preconditioned dogs not given L-NAME); none of the animals survived reperfusion (incidence of VF 100%). The improvement in the severity of the degree of in homogeneity which resulted from preconditioning was abolished by L-NAME administration.5. L-NAME itself elevated blood pressure (from 96 +/- 5 mmHg diastolic to 119 +/- 7 mmHg), reduced heart rate (from 155 +/- 7 to 144 +/- 4 beats min-') but did not change LVEDP, LVdP/dt,,,,, coronary blood flow, ST-segment elevation or the degree of inhomogeneity of conduction. When given 10 min before the prolonged coronary artery occlusion in dogs not subjected to preconditioning, L-NAME had no significant effect on the severity of arrhythmias except for more periods of VT (a mean of 11.7 +/- 4.7episodes per dog).6. It is concluded from these studies that the generation of nitric oxide contributes to the marked antiarrhythmic effects of preconditioning in the canine myocardium, probably through elevation of cyclic GMP.

Animals↗

Fibrosarcoma of the transverse colon.

Colonic fibrosarcoma is extremely rare. This is a report of a patient with fibrosarcoma of the transverse colon, manifesting as an obstructive lesion with local perforation and abscess formation.

Colon↗

Antiarrhythmic effects of Org 6001 in rats: correlation with plasma and tissue drug concentrations.

The antiarrhythmic effects of Org 6001 following oral administration in the rat have been assessed and correlated with plasma, myocardial and skeletal muscle drug concentrations. Arrythmias were induced by coronary artery ligation in anaesthetized rats. Org 6001 (10, 20, 50 and 100 mg/kg given 1 h before ligation) significantly reduced mortality and the incidence of ventricular fibrillation in the 0-30 min post ligation period. Only the highest dose of drug also significantly reduced the number of ventricular ectopic beats following ligation. A linear relationship was observed between the oral dose and the Org 6001 concentrations in plasma and skeletal muscle determined 90 min after drug administration. The Org 6001 concentration in the myocardium was not linearly related to the administered dose and Org 6001 appeared to be concentrated to a higher extent in cardiac than in skeletal muscle at that time. No statistically significant difference in drug levels in the ischaemic left ventricle and normal right ventricle plus septum was observed. The antiarrythmic effect of Org 6001, as measured by changes in the incidence of ventricular fibrillation, correlated with myocardial concentrations of the drug.

Androstanols↗